Using novel molecular approaches to understand transmission of Mycobacterium leprae in the Comoros

This PhD thesis centers around the complex dynamics of leprosy, a debilitating disease caused by Mycobacterium leprae (M. leprae). Despite being among the first human pathogens identified, the means by which it spreads among individuals remain enigmatic, complicating leprosy control even with available treatments. With an annual diagnosis of over 200,000 new cases worldwide and a significant proportion children, indicating the ongoing spread of the disease. Innovative approaches to leprosy control are essential to definitively halt transmission. This study revisited transmission questions in an innovative manner. Initially, it examines the specificity of RLEP qPCR for M. leprae. Subsequently, it evaluated non-invasive, field-applicable tests to quantify bacterial levels in patients. Findings show that αPGL-I IgM levels in fingerstick blood correlate with bacterial load. Combining αPGL-I R-values ≥ 0.81 with a lesion count ≥25 predicts high bacterial load in a patient. Pioneering the field, the study introduced targeted Next Generation Sequencing of M. leprae through the innovative Deeplex Myc-Lep assay with a detection limit of 80 M. leprae genomes. This approach enabled the first drug resistance survey of M. leprae in the Comoros, revealing no drug resistance. The Deeplex Myc-Lep also characterized M. leprae diversity in the Comoros, classifying distinct genotypes linked to patient residences, aiding in understanding transmission patterns. SNP subtypes detected are 1D-Malagasy and 1A. Among 265 patients with a full VNTR pattern, 79.7% cluster with at least one other patient based on identical VNTR profiles. Additionally, the study explored if wild ticks from the Comoros carry M. leprae DNA, building on earlier evidence of their potential to transmit the bacterium. No M. leprae DNA is detected in these ticks, suggesting a limited role in leprosy transmission. These insights contribute to refining strategies for effective leprosy control, within the Comoros and beyond.